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US20110282192A1 - Multimodal depth-resolving endoscope - Google Patents

Multimodal depth-resolving endoscope Download PDF

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US20110282192A1
US20110282192A1 US13/146,955 US201013146955A US2011282192A1 US 20110282192 A1 US20110282192 A1 US 20110282192A1 US 201013146955 A US201013146955 A US 201013146955A US 2011282192 A1 US2011282192 A1 US 2011282192A1
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oct
optical
imaging
endoscope according
tissue
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Noel Axelrod
Amir Lichtenstein
Gabby Sarusi
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0093—Detecting, measuring or recording by applying one single type of energy and measuring its conversion into another type of energy
    • A61B5/0095—Detecting, measuring or recording by applying one single type of energy and measuring its conversion into another type of energy by applying light and detecting acoustic waves, i.e. photoacoustic measurements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/00064—Constructional details of the endoscope body
    • A61B1/00071—Insertion part of the endoscope body
    • A61B1/0008—Insertion part of the endoscope body characterised by distal tip features
    • A61B1/00096—Optical elements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/00163—Optical arrangements
    • A61B1/00172—Optical arrangements with means for scanning
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0033—Features or image-related aspects of imaging apparatus, e.g. for MRI, optical tomography or impedance tomography apparatus; Arrangements of imaging apparatus in a room
    • A61B5/0035—Features or image-related aspects of imaging apparatus, e.g. for MRI, optical tomography or impedance tomography apparatus; Arrangements of imaging apparatus in a room adapted for acquisition of images from more than one imaging mode, e.g. combining MRI and optical tomography
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0062—Arrangements for scanning
    • A61B5/0066—Optical coherence imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters
    • A61B5/0086—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters using infrared radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/6852—Catheters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A61B2018/2035—Beam shaping or redirecting; Optical components therefor
    • A61B2018/20351—Scanning mechanisms
    • A61B2018/20359—Scanning mechanisms by movable mirrors, e.g. galvanometric
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A61B2018/2065—Multiwave; Wavelength mixing, e.g. using four or more wavelengths
    • A61B2018/207—Multiwave; Wavelength mixing, e.g. using four or more wavelengths mixing two wavelengths
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A61B18/22—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
    • A61B2018/2205—Characteristics of fibres
    • A61B2018/2211—Plurality of fibres
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy

Definitions

  • the present invention relates to endoscopy in general and to depth-resolving, multimodal endoscopy in particular.
  • Endoscopy is a vital, yet minimally invasive, operative procedure, increasingly employed for both diagnosis and management of many medical and surgical conditions.
  • the first endoscope developed in the 1960s uses a long flexible fiber-optic coupling between the remote lesion site and the user. This gives adequate diagnostic information, although the image quality may be compromised by both the number of (intact) elements within the fiber bundle and the light losses, which become significant when the individual fibers of a bundle decrease below 6-8 ⁇ m diameter.
  • An alternative class of endoscope uses a thin rigid tube enclosing a distributed lens system. These instruments are optically superior to their fiber bundle counterparts, although their use is confined to regions of the body that afford reasonably straight line access to the region of interest or keyhole surgical access, e.g. imaging ports in laparoscopic surgery.
  • the image contrast in these instruments originates from the surface and subsurface regions of the translucent tissue under examination.
  • Depth-resolving imaging is required in surgery, neurosurgery, orthopedic, for dentist and oral surgeon, gynecology, cardiology, etc
  • Depth-resolving imaging is a well-established technique in biomedical imaging. This includes multi-spectral microscopy, two-photon microscopy, Optical Coherence Tomography (OCT), photoacoustic imaging and some other techniques. They differ in the physical principles of the underlying image contrast mechanism, image resolution and penetration depth.
  • OCT Optical Coherence Tomography
  • Multi-spectral microscopy relies on optical contrast at different light wavelength, while OCT relies on optical scattering of ballistic photons and photoacoustic on optical absorption.
  • One of the system modalities is an endoscopic multi-spectral microscopy that enables high resolution imaging of the surface at different wavelengths of light.
  • Multi-spectral imaging is currently in a period of transition from its role as an exotic technique to its being offered in one form or another by all the major microscopy manufacturers. This is because it provides solutions to some of the major challenges in fluorescence-based imaging, namely ameliorating the consequences of the presence of autofluorescence and the need to easily accommodate relatively high levels of signal multiplexing. MSI, which spectrally characterizes and computationally eliminates autofluorescence, enhances the signal-to-background dramatically, revealing otherwise obscured targets. Some technologies used to generate multispectral images are compatible with only particular optical configurations, such as point-scanning laser confocal microscopy.
  • Band-sequential approaches such as those afforded by liquid-crystal tunable filters (LCTFs) can be conveniently coupled with a variety of imaging modalities, which, in addition to fluorescence microscopy, include brightfield (nonfluorescent) microscopy as well as small-animal, noninvasive in-vivo imaging.
  • Brightfield microscopy is the chosen format for histopathology, which relies on immunohistochemistry to provide molecularly resolved clinical information.
  • fluorescent labels multiple chromogens, if they spatially overlap, are much harder to separate and quantitate, unless MSI approaches are used.
  • In-vivo imaging is a rapidly growing field with applications in basic biology, drug discovery, and clinical medicine.
  • the sensitivity of fluorescence-based in-vivo imaging, as with fluorescence microscopy, can be limited by the presence of significant autofluorescence, a limitation which can be overcome through the utilization of MSI.
  • OCT is a well established imaging technology that produces high resolution cross-sectional images of the internal microstructure of living tissue.
  • the superb optical sectioning ability of OCT which is achieved by exploiting the short temporal coherence of a broadband (white) light source, enables OCT scanners to image microscopic structures in tissue at depths beyond the reach of conventional bright-field and confocal microscopes. Probing depths exceeding 2 cm have been demonstrated in transparent tissues, including the eye and the frog embryo. In the skin and other highly scattering tissues, OCT can image small blood vessels and other structures as deep as 1-2 mm beneath the surface.
  • Photoacoustic imaging does not rely on ballistic photons for excitation; and ultrasonic waves have 2-3 orders of magnitude weaker scattering than optical waves in biological tissues. Consequently, photoacoustic imaging provides high resolution at relatively large imaging depth. Therefore, photoacoustic imaging combines the advantages of optical absorption contrast with ultrasonic spatial resolution for deep imaging beyond the ballistic regime.
  • Photoacoustic microscopy is a hybrid technique that detects absorbed photons ultrasonically through the photoacoustic effect.
  • a short-pulsed laser irradiates biological tissues
  • wideband ultrasonic waves referred to as photoacoustic waves
  • the magnitude of the photoacoustic waves is proportional to the local optical energy deposition and, hence, the waves divulge physiologically specific optical absorption contrasts.
  • optical energy deposition is related to the optical absorption coefficients of pigments, concentrations of multiple pigments can be quantified for functional imaging by varying the laser wavelength.
  • ultrasonic imaging can provide better spatial resolution than pure optical imaging when the imaging depth is beyond one optical transport mean-free-path ( ⁇ 1 mm).
  • PAM uses neodymium-doped yttrium aluminum garnet (Nd:YAG) laser with about 10-ns laser pulses to generate photoacoustic waves.
  • Laser light at a designated wavelength is delivered through an optical fiber to the photoacoustic (PA) microscope scanner. The energy of each laser pulse is detected by a photodiode for calibration.
  • PA photoacoustic
  • the system is a flexible fiber optic endoscope with optical Microelectromechanical systems (MEMS) Scanning micromirror head (MEMS Head).
  • MEMS Microelectromechanical systems
  • MEMS Head Microelectromechanical head
  • MEMS have enabled the miniaturization of scanning mirrors for placement at the distal end of fiber-based scanning microendoscopes.
  • Other applications for beam-scanning micromirrors include image displays and optical switches.
  • a miniature scanning confocal microscope using two single-axis micromirrors was proposed and demonstrated by Dickensheets and Kino (D. L. Dickensheets and G. S. Kino, “Silicon-micromachined scanning confocal optical microscope,” J MEMS 7, 38-47 (1998)).
  • This compact module achieved high resolution confocal imaging at 20 frames/second over a 90 ⁇ m ⁇ 90 ⁇ m field of view with a 1.1 mm working distance and 0.25 numerical aperture.
  • More recent advances in scanning technology for confocal microscopy include three-dimensional dimensional scanning deformable micromirrors (Y. Shao and D. L. Dickensheets.
  • MEMS three-dimensional scan mirror in SPIE MOEMS Display and Imaging Systems II (SPIE, San Jose, Calif., 2004), pp. 175-183) and micromirrors for dual-axes confocal microscopy (H. Ra, Y. Taguchi, D. Lee, W. Piyawattanametha, and O. Solgaard. “Two-dimensional MEMS scanner for dualaxes confocal in vivo microscopy,” in Tech. Digest of IEEE International Conference on MEMS, (IEEE, Turkey, 2006), pp. 862-865) and tandem video-rate confocal microscope (Watson T. F., Neil M. A. A., Juskaitis R., Cook R. J. Wilson T., “Video-rate confocal endoscopy.”, Journal of Microscopy, Vol. 207, Pt 1 July 2002, pp. 37-42).
  • MEMS scanning confocal microscopes have also been fabricated using electrostatically actuated microlenses for focusing and scanning. Many technologies have been explored to miniaturize confocal microscopes. High deflection MEMS scanners can provide fast scanning and high resolution imaging, using appropriate lens systems, in a compact package.
  • MEMS mirrors have also been used for endoscopic OCT.
  • Ex vivo OCT imaging of rat bladder has been accomplished using a single-axis MEMS mirror.
  • More recent advances in scanning technology for OCT microscopy include 3D imaging with two axes scanning SOI MEMS micromirror.
  • the present invention relates to a modular endoscope unit which is insertable into all bodily cavities and is comprised of a flexible and guidable tube, leading a laser irradiation into a miniature head that injects electromagnetic radiation onto its target and collects the returning electromagnetic radiation and acoustic transients.
  • the endoscope is intended for real time biomedical imaging in vivo and in situ of cells, living tissues, of organs and bodily cavities for diagnostic purposes, morphological, physiological and biochemical investigation.
  • the system is an instrument that bridges form and functions and allows following the dynamics of the living cells tissues and organs of the living body.
  • Both imaging and surgery capabilities are generated by an ultrashort laser pulses that generate single photon or multiple photon (MP) excitation (irradiation) which is focused on the desired target by a focusing system designed for focusing divergent incident light beams on a common point on the sample face or inside the tissue.
  • MP multiple photon
  • the system may provide in-depth imaging of a thick sectioned tissue which is kept alive and must be kept intact.
  • the imaging system enables in-depth resolving capabilities for the detection of undersurface pathologies and structures such as blood vessels, urine vessels etc that lie under the tissue surface, during minimal invasive surgery procedures thus providing a safety margin for the surgeon.
  • the endoscope may be used for the targeted in-depth and site restricted photobleaching, ablation or surgery without harming the surface and the tissue lying outside the plan of the focused radiation, of a living inhomogeneous tissue either sectioned or of an intact living body.
  • Multiphoton excitation imaging relates to high harmonic generation of photons interacting nearly simultaneously (within 10- 18 sec) with a nonlinear medium (no inversion symmetry). Deep tissue imaging is achieved with the longer (IR) wavelengths (700-1000 nm) that scatter considerably less than the equivalent single photons (350-500 nm) and allows penetration into inhomogeneous tissue while photodamage is restricted to the focal plane where the incident rays meet to enable the high harmonic event to happen.
  • IR IR
  • the present invention thus relates to a fiber-optic multimodal endoscope, comprising:
  • an optical coherent tomography (OCT) module comprising: an OCT light source, a fiber-optic Michelson interferometer, and an OCT detector;
  • a photoacoustic (PA) module comprising: a short pulsed PA light source, optical fibers, a PA detector, and an ultrasound transducer;
  • said PA light source and said OCT light source are coupled to said endoscopic head through said optical switcher, and said endoscopic head controls the PA light source and the OCT light source, so that the endoscopic head injects electromagnetic radiation onto a target and then collects returning electromagnetic radiation and acoustic transients from the target.
  • the multimodal endoscope further comprises a multi-spectral imaging (MSI) module comprising: a broadband light source, collimated optics, and a color CCD/CMOS camera focal plan array, wherein said broadband light source is coupled to said endoscopic head through said optical switcher.
  • MSI multi-spectral imaging
  • the head comprises a Micro-Opto-Electro-Mechanical Systems (MOEMS) scanning module.
  • MOEMS Micro-Opto-Electro-Mechanical Systems
  • the multimodal endoscope provides in-depth images for the detection of undersurface pathologies or structures.
  • the in-depth images are 3-dimensional images of 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 millimeters (mm) under tissue surface pathologies or structures.
  • the undersurface pathologies or structures comprise: large and small blood vessels, urine vessels, major nerves, bile ducts, or cartilage.
  • the multimodal endoscope further comprises a high power short pulsed laser light source that generates single photon or multiphoton (MP) excitation which are focused on a desired target by a focusing system designed for focusing divergent incident light beams on a common point on a sample face or inside a tissue.
  • MP multiphoton
  • the multiphoton excitation is a two-photon excitation which provides deep tissue imaging via longer Infra-Red (IR) wavelengths of 700 nm to 1000 nm that scatter considerably less than the equivalent single photons of 350 nm to 500 nm wavelengths, allowing deeper penetration into inhomogeneous tissue, and wherein photodamage is restricted to the focal plane where the incident beams meet when two photons meet almost simultaneously within 10-18 seconds.
  • IR Infra-Red
  • the focusing is done through the usage of two micro-sized resonating mirrors moved by two autonomous microelectromechanical systems (MEMS), both MEMS enabling focusing the two incident beams on a target, fixedly or in a rastering fashion.
  • MEMS microelectromechanical systems
  • the rastering is achieved by the rapid scanning of the focused laser beam in two dimensions, the X and the Y axis; the X-axis micro mirror achieving a 10 MHz-15 MHz frequency while the slow Y axis achieves a 15 Hz-50 Hz frequency, thus a high video rate of 60 Hz. may be accomplished.
  • the PA, OCT and MSI modalities may operate simultaneously or be switched from one imaging modality to another using the optical switch without removing the endoscope inserted into a body.
  • the OCT light source is a swept source.
  • the fiber-optic Michelson interferometer comprises a 2 ⁇ 2 beam-splitter, an A-Scan or M-scan mirros, fiber optics and a MOEMS spectrometer.
  • FIG. 1 shows a schematic illustration of a multimodal endoscoping system according to one embodiment of the invention, combining Photoacoustic (PA), Optical Coherence Tomography (OCT) and Multi-Spectral (MS) imaging modalities, wherein all modalities are connected to an endoscopic head via fiber optics and an optical switcher.
  • PA Photoacoustic
  • OCT Optical Coherence Tomography
  • MS Multi-Spectral
  • FIG. 2 depicts a scheme of the Microelectromechanical Systems (MEMS) based multimodal endoscope head comprising a MEMS scanner shown in FIG. 1 .
  • MEMS Microelectromechanical Systems
  • FIG. 3 is a schematic illustration of a forward-looking endoscopic Micro-Opto-Electro-Mechanical Systems (MOEMS) head module equipped with a MEMS scanner. All parts are designed to be aligned by location in tight tolerance polyimide tubing.
  • MOEMS Micro-Opto-Electro-Mechanical Systems
  • FIG. 4 shows a block diagram of the architecture of the Multimodal Endoscopic System of the invention comprising a MOEMS scanning module equipped with a MEMS scanner unit with control electronics (ASIC) that is responsible for synchronization of lasers and MEMS scanner.
  • ASIC control electronics
  • FIG. 5 is a scheme of a Fourier domain optical coherence tomography (FD-OCT) microscopy in an endoscope.
  • a swept source outputs a light that is directed both to an endoscopic reference arm and to an endoscopic detection (sample) arm connected to the Multimode Endoscopic Scanning Head (MESH) system.
  • MEH Multimode Endoscopic Scanning Head
  • FIG. 6 shows a general scheme of an endoscope based photoacoustic mode of the invention.
  • the present invention relates to a fiber-optic multimodal (multi-spectral, Optical Coherence Tomography, photoacoustic) endoscope with beam scanning by a two-dimensional (2D) MEMS scanner present in the endoscopic head.
  • FIG. 1 shows the three imaging modalities (PA, OCT, and MS) combined in a synergetic way in a single endoscopic system.
  • the PA, OCT and MS light sources are coupled to the endoscopic head through an optical switcher.
  • FIG. 2 is a close-up of the endoscopic head shown in FIG. 1 .
  • the endoscope of the invention is capable of sequential or parallel multi-spectral, OCT and photoacoustic imaging.
  • the endoscope provides real-time imaging with a rate of 5 to 60 frames per second for each of the three imaging modalities.
  • FIG. 3 illustrating schematics of a forward-looking endoscopic head unit equipped with a MEMS scanner.
  • the outer diameter of the tubing is about 4 mm- 6 mm. All parts are designed to be aligned by location in tight tolerance polyimide tubing.
  • the Silica Spacer is used for optical coupling between the single mode fiber and collimating lenses (shown as “Lens 1 ” and “Lens 2 ”).
  • the Spacer polyimide is used as a mold material for the collimating lenses.
  • the Fold Mirrors are used for redirecting the optical beam to a forward-looking configuration illustrated in FIG. 2 showing the light beam exiting from the endoscopic head in a straight line (and not sideways), on the side marked by “Envelope”.
  • the scanning head illustrated in FIG. 3 uses a single mode optical fiber (shown as “SM Fiber”) for the illumination.
  • SM Fiber single mode optical fiber
  • the illumination light exiting the fiber is collimated by a pigtailed collimator to a beam diameter of about 0.5 mm, matched to the micromirror diameter.
  • the MEMS micromirror scans the beam in the horizontal direction at the resonance frequency of the inner axis of the mirror, and in the vertical direction at a low frequency using the outer axis.
  • An objective shown as “Lens 3 ” (lens achromatic duplet) is used to form an image of the micromirror in the entrance aperture of the objective lens. These two lenses are selected to magnify the beam size and improve resolution without significantly compromising the scan angle and field of view.
  • An adaptive optics system can be obtained by placing a variable-focus lens at the exit aperture of the head.
  • the optics of the MESH head is designed for minimization chromatic aberrations to allow broad band propagation. This is achieved by use of achromatic optics. Backscattered light is recollected and focused into the optical fiber by the same optical system.
  • the scanner used in the MESH is a suspended micromiRror with two-degree freedom. It is actuated by vertical, electrostatic combdrive actuators.
  • the scanner is fabricated by performing deep-reactive ion etching (DRIE) process on a double SOI wafer.
  • the mirror size may be about 500 ⁇ 500 ⁇ m 2 .
  • the inner axis of the mirror is controlled with an AC voltage signal at the resonance frequency of the mirror about 10-15 kHz, and the corresponding optical deflection is approximately ⁇ 6-9 degrees.
  • the outer axis is actuated with a low frequency saw tooth wave at 10-50 Hz, with a voltage scan yielding an optical deflection of 6-9 degrees.
  • One of the key features of the proposed multimodal endoscope is use of a unit optical module (MESH system) for the three depth-resolving imaging modalities.
  • the components laser, detectors, optics
  • the switching between different modes can be done in real time using optical switch technology between single mode fiber from a laser source of a given mode and the MESH system.
  • FIG. 4 showing an embodiment of an architecture of the Multimodal Endoscopic System, which comprises a MOEMS scanning module with a MEMS scanner unit with control electronics (ASIC) that is responsible for synchronization of lasers (shown as “Lasers Sync” box) and driving and controlling (shown as the “MEMS Drive & Cntr” box) the MEMS scanner.
  • the output signal from the detectors goes to an image frame grabber and an imaging algorithm to display a combined depth-resolved image of the tissue interrogated by the laser sources.
  • Input/Output is the driver and software interface between an external computer connected to the endoscope and the ASIC of the MOEMS scanning module. Switching between OCT/PA and multispectral imaging modalities is performed during procedure by the operator or automatically, via a controller in the external computer which in turn drives the optical switcher.
  • ASIC is the control electronics units (dye chip) which are a part of the MOEMS scanning module.
  • the ASIC chip is electrically connected to the MEMS scanner, to the laser drivers and to the external computer.
  • ASIC consists of the MEMS drive and control module that are responsible for synchronization of the scanning micromirror with the lasers and laser synchronization unit.
  • the ASIC performs monitoring of the precise position of the mirror by use of MEMS position sensors. This allows achieving the desired accuracy in direction of the laser beams to obtain high resolution OCT/PA imaging.
  • ASIC controls the OCT and PA laser sources (shown as “OCT/PA Lasers” box) through the laser drivers (shown as “Laser Drivers” box).
  • microsecond accuracy is needed to switch on/off laser beam output.
  • high accuracy is required for positioning micromirror about X and Y axis.
  • OCT/PA Optics shown as “Optics” box in the Optical Module
  • a laser beam from the PA/OCT source is coupled to the fiber by an optical collimator.
  • the fiber is connected to the endoscopic head through the optical switcher.
  • the endoscopic head ( FIG. 2 ) comprises a single mode fiber, collimator lenses, static mirror, and objective micro lens.
  • the heater of the MEMS Scanner (shown as “MEMS Scanner” box) is the two axis scanning micromirror.
  • the scan rate, amplitude and precise position are controlled by the ASIC.
  • the laser beam from the OCT source is focused on the tissue through the objective lens; the reflected light is collected by the same objective lens and is passed in the backward direction through the same optical path as in the forward direction and finally goes to the detector arm of the interferometer (2 ⁇ 2 coupler) to the photodetector (shown as “Detector OCT” box).
  • the signal from the photodetector is collected by the data computer acquisition board and processed to form OCT image.
  • the photodetector is a part of the endoscopic system but placed outside the endoscopic head.
  • the short-pulsed laser beam from PA source is focused through the collimator underneath the tissue surface. It generates a high-frequency ultrasound signal that is detected by the ultrasound detector (shown as “Detector PA” box).
  • the ultrasound detector is a piezoelectric detector in the needle configuration; it is placed on the tissue side and electrically connected to the frame grabber of the computer (shown as “Image frame grabber and computer control software”).
  • Multispectral imaging A light beam from a broadband source is passed through a tunable filter and collimated to the optical fiber. This light beam is coupled to the endoscopic head through the optical switcher. Inside the endoscopic head the light beam is projected through the same optical path as in the case of OCT mode. In contrast to the OCT mode the light beam is focused on the tissue surface. The focusing can be implemented by use of the variable focus lens objective. The light reflected from the tissue goes in a backward direction through the same optical path. It is collected by the photodetector. The detector is placed on the detector arm through a 2 ⁇ 1 beam-splitter outside the endoscopic head. The signal from the photodetector is acquired by the computer.
  • a high-power very short-pulsed laser source is used.
  • the light from the high-power very short-pulsed laser source is coupled through an optical collimator to the optical fiber.
  • the light passes through the optical switcher to the endoscopic head. Inside the endoscopic head, the light passes through the same optical path as in case of other modalities and focuses on the interrogated tissue.
  • the computer in this mode controls through the ASIC the exact direction of the light beam.
  • the section below provides a more detailed OCT, PA imaging modalities and two-photon absorption surgery description.
  • the description of the multi-spectral imaging is omitted since this mode differs insignificantly from the visual mode implemented in existing endoscopes.
  • the main difference from the visual mode is implementation of a tunable filter on the optical path length to acquire images at different wavelengths and image processing software that combines these images in the integrated way.
  • OCT mode OCT is attracting interest among the medical community, because it provides tissue morphology imagery at much higher resolution (better than 10 ⁇ m) than other imaging modalities such as MRI or ultrasound.
  • FDOCT Fourier domain OCT
  • SSOCT swept source OCT
  • SSOCT has the advantage of a simple system setup, low cost, and capability of balanced detection.
  • mirror image and autocorrelation noise can be removed instantaneously by the simple addition of an electro-optic modulator.
  • FIG. 5 showing a schematic diagram of the FDOCT system based on the built swept source.
  • the output light from the swept source is split into a reference arm and a detection (sample) arm by a 2 ⁇ 2 beam-splitter (also called coupler).
  • the fiber optics, 2 ⁇ 2 beam splitter, A-Scan (amplitude modulation scan) and MOEMS are referenced together as a Michelson interferometer.
  • the reference arm comprising an A-Scan unit is used to scan optical pathlength in the reference arm of the Michelson interferometer, rapidly and precisely.
  • the pathlength must be varied over a distance large enough to cover the desired axial imaging range, which may be as large as a centimeter or more for ocular imaging and 2 mm for imaging skin and other optically dense tissues, and its positioning inaccuracy must be a fraction of the source coherence length.
  • the desired scanning speeds can be attained by using a piezoelectric transducer to drive a parallel minor system in which light reflects multiple times (Y. Pan, E. Lankenau, J. Welzel, R. Birngruber, and R. Engelhardt, “Optical coherence-gated imaging of biological tissues,” IEEE J. Select. Topics Quantum Electron., vol. 2, pp. 1029-1034, 1996).
  • the signal from the balanced detector is converted by a data acquisition board.
  • the number of data points for each A-line data acquisition during the frequency scan is about 1,000.
  • the detected fringe signal is transformed from time to frequency domain with the swept spectral function (R. Huber, M. Wojtkowski, K. Taira, J. G. Fujimoto, and K. Hsu, Opt. Express 13, 3513 (2005)).
  • the OCT image is formed from the processed spectral signal at each pixel of the focus plane.
  • FIG. 6 showing a general scheme of an endoscope based photoacoustic mode (PAM) of the invention.
  • PAM photoacoustic mode
  • 10-ns laser pulses shown as “Pulsed Laser” box
  • a tunable dye laser pumped by a Nd:YAG laser or mode-locked fiber-laser in other arrangement
  • Laser light at a designated wavelength is delivered through an optical fiber (shown as “Fiber”) to the endoscopic MESH system (shown as “Endoscopic Head” and shown in more detail in FIG. 3 ).
  • the energy of each laser pulse is detected by a photodiode for calibration.
  • the laser beam from the fiber is weakly focused into the tissue to avoid tissue overheating.
  • the generated photoacoustic wave is collected by ultrasonic transducer (or transducers) that is in contact with the tissue about 2-10 cm away from the irradiating region.
  • the transducers can be a part of the endoscopic head (to be placed at the tip of the endoscopic head and thus in contact with the tissue).
  • a needle-type ultrasonic hydrophone with the bandwidth up to 20 MHz is inserted into the tissue.
  • the optical focus of the laser beam is about 100 ⁇ m in diameter.
  • the ultrasonic transducer or transducers are used with a large numerical aperture (NA) ultrasound lens, a high central frequency and a wide bandwidth for achieving high spatial resolution.
  • NA numerical aperture
  • the system provides a raster scanning of lateral (x-y) plane with a step size of about 100 ⁇ m.
  • the scan area is about 2 ⁇ 2 mm (3 ⁇ 3 mm for 9 0 tilt).
  • the pulse repetition rate is about 325 kHz to achieve 8 Hz frame rate.
  • the high frequency scanner mirror can be used to study axon activity and metabolism as a tool in learning neuron physiology and pathology, thus providing information about tissue conductivity.
  • the high frequency scanner mirror can be used to study axon activity and metabolism as a tool in learning neuron physiology and pathology, thus providing information about tissue conductivity.
  • Another technique that can be used with the endoscope according to the invention is the two-photon absorption surgery and imaging method.
  • An object of this technique is to acquire tissue ablation for microsurgery.
  • This can be achieved by the two-photon excitation phenomenon whereby a chemical group capable of selectively absorbing a specific lightwave (chromophore) absorbs two photons nearly simultaneously (within 10 ⁇ 18 sec), where each photon is twice the wavelength (half the energy) of a single photon needed to excite the chromophore.
  • This process is termed nonlinear excitation since when a fluorophore is excited it emits with intensity which is proportional to the square of the excitation intensity (three photons emission is cubed).
  • the light source is a high-power, short pulsed laser such as the Ti-sapphire laser.
  • the probability of the simultaneous absorption is proportional to the product of the pulse repetition rate and the pulse duration.
  • shortening the pulse duration and/or reducing the pulse rate increases the probability of two photons generation.
  • in mode locked Ti-sapphire laser pulse duration is ⁇ 100 fsec.
  • the longer infrared (IR) photons (700-1000 nm) are less damaging and induce less phototoxic effects in the cells. They scatter considerably less than the shorter ones (350-500 nm) allowing deeper penetration into inhomogeneous tissue. This enables optical sectioning and deep penetration within thick tissue by targeting the volume of the tissue to be ablated at a required depth by the focusing of two lower energy photons that together produce a very damaging ultraviolet (UV) wavelength ( ⁇ 300 nm).
  • UV ultraviolet
  • Directing of the ablation beam is done by the same MEMS micromirror that is also used for imaging (confocal, photoacoustic, OCT). Focusing is done by the variable focus length lens.
  • the advantage of the two-photon absorption method for surgery is that the two-photon event occurs only in illuminating a small volume at the focal point instead of the hourglass volume usually achieved by a single photon, thus avoiding one of the drawbacks of confocal microscopy, i.e., the excitement of the specimen above and below the focal plane.
  • a volume lesser than 1 femtoliter with ⁇ 1- ⁇ m resolution in the Z direction was achieved with a theoretically sub-cellular resolution.
  • Another innovative application is imaging of the retina, in which the two-photon focusing technique is able to excite a chromophore present only at the focal point, whereas same photoreceptors do not respond to longer IR wavelengths above or below ablation of damaged tissue at the bottom of the retina might be produced.
  • Another application of two-photon microscopy is two-photon photolysis of trapped species that, when excited by light, turn from being inert to active. For example, immediate release of Ca +2 ions from the photolabile calcium chelator DM-nitrophen (Parthasarathy. K, (2006), J. Clin. Invest., 116: 2193-2200). Rapid release of calcium ions from its cages was exploited to investigate the role of intracellular Ca +2 microdomains in regulation of calcium ions sensitive processes.
  • the multimodal endoscope of the present invention has many applications in diagnostics and surgery in different field of Medicine. For example, in cancer surgery, where it can show the tumor borders and demonstrate neovascularization and navigate the surgeon such as to avoid damaging vital structures; in orthopedics, to show cartilage smoothness, early damage to connective tissue, or ligaments with internal (undersurface) damages; to show to the dentist or oral surgeon the abscess and his fistula online; to measure the sinus and the bone thickness; to demonstrate nerve bundle for preventing damage.
  • the multimodal endoscope of the invention can be used for detecting one or more of the following pathologies:

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